This is the third submission of a competitive renewal of an R01. Originally titled "Eye Movements: Children of Schizophrenics," we have re-titled to application to "Childhood Physiology and Risk for Schizophrenia," to more accurately represent the expansion of goals in this resubmission. An increasingly important issue for child psychiatry has been to develop strategies for the primary prevention of schizophrenia. This clinical issue is mirrored in a correspondingly fundamental biological issues: "When" during development does alteration in brain development occur, "What" is the alteration in brain development, and "Why" does the alteration occur (what are the genetic and environmental etiologic factors)? It is hoped that answers to these Where, What, and Why questions will guide decisions on "How" we can intervene to normalize brain development and reduce risk for schizophrenia. The first five years of this project focused on the When question, utilizing a basic physiological phenotype, smooth pursuit eye movements (SPEM), to demonstrate that at least one component of schizophrenia associated brain dysfunction is fully expressed by 6 years of age. A specific measure, the frequency of leading saccades during SPEM, is sensitive and specific to genetic risk for schizophrenia, and is fully expressed by 6 years of age. The leading saccade measure is normalized, in adults, by acute nicotine exposure, supporting nicotinic mechanisms as part of the Why does this happen. This competitive renewal is designed to extend these findings. Physiological measures, and in particular, sensory gating of the P50 auditory evoked potential, will be examined in a longitudinal study of young infants to explore when the ability to screen sensory information develops (Specific Aim # 1). The role of nicotine (tobacco) in this early developing sensory gating capacity will be examined in infants whose mothers smoke (Specific Aim #2). Clarification of these developmental issues will allow whether physiological measurements of genetic vulnerability to psychosis can be identified in the young infant (Specific Aim #3). Clarification of this methodology may lead to a novel prenatal intervention strategy designed to decrease risk for adolescent and adult onset of psychosis.